ABSTRACT Heart failure with preserved ejection fraction (HFpEF) is a syndrome that is particularly difficult to diagnose and treat, yet, it is estimated to affect >50% of patients with HF. With >1 million hospitalizations for HF in the U.S. annually and one-year mortality rates up to 29%, the health and economic impact of HFpEF is substantial. The early detection of volume overload in the outpatient setting is critical to optimize decongestive therapy prior to frank decompensation requiring hospitalization. Pulmonary congestion, a hallmark of volume overload in HFpEF, plays a central role in the progression of decompensation ultimately leading to hospital admission. However, current diagnostic methods for its detection are insensitive. Our central hypothesis is that the assessment of pulmonary congestion by lung ultrasound (LUS) in HFpEF will outperform currently available approaches. LUS is a novel, non-invasive and inexpensive tool in the quantification of pulmonary congestion. With this study, we will expand our prior work to understand how this method could be utilized in an ambulatory setting to identify pulmonary congestion in patients with known or suspected HFpEF. Our long-term goal is to initiate early intervention, improve quality of life, and reduce HF hospitalizations and costs in this population. Our specific aims are: 1) Determine the prevalence of lung ultrasound findings of pulmonary congestion and their echocardiographic, biomarker and quality of life correlates in patients with HFpEF. 2A) Investigate the prognostic value of lung ultrasound-detected pulmonary congestion for adverse HF events in ambulatory patients with HFpEF. 2B) Develop and validate a congestion-focused risk score for ambulatory patients with HFpEF integrating clinical, ultrasound and biomarker findings. Our approach is innovative by focusing on new approaches to volume status assessment in a traditionally difficult to diagnose cohort of HFpEF patients, and employing an inexpensive point-of-care device paired with a time-efficient, easily learned imaging protocol. This proposal is significant because it will provide critically important information regarding the incremental value of LUS for the detection of pulmonary congestion in ambulatory patients with HFpEF. It is therefore a critical step toward improving the early detection of volume overload in patients at high risk for HF hospitalizations and the associated morbidity, mortality and cost.